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Association of antiviral prophylaxis and rituximab use with posttransplant lymphoproliferative disorders (PTLDs): A nationwide cohort study.

ABSTRACT: Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein-Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation, and outcome of histologically proven PTLD. We included 4765 patients with a follow-up duration of 23 807 person-years (py). Fifty-seven PTLD cases were identified; 39 (68%) were EBV positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years posttransplant were 3.51, 2.24, and 1.75/1000 py and 0.44, 0.25, and 0.29/1000 py for EBV- PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199-1.436], p = .264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751-6.521], p = .150). However, none of the patients (0/191) who received a rituximab-containing induction treatment experienced PTLD, but 57 of 4574 patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD-free survival was significantly longer (0.104 years [95% CI 0.077-0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD.

SUBMITTER: Walti LN

PROVIDER: S-EPMC8359347 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation. Histologic heterogeneity and a lack of treatment standards have made evaluating clinical outcomes in specific patient populations difficult. This systematic literature review investigated the impact of the PTLD histologic subtype on survival in a large data set. METHODS:Case series were identified on PubMed with the search terms post-transplant lymphoproliferative disorder/disease, PTLD, and solid organ transplantation, with additional publications identified through reference lists. The patient characteristics, immunosuppressive regimen, treatment, survival, and follow-up time for 306 cases were extracted from 94 articles, and these cases were combined with 11 cases from Emory University Hospital. Patients with a recorded subtype were included in a Kaplan-Meier survival analysis (n = 234). Cox proportional hazards regression analyses identified predictors of overall survival (OS) for each subtype and B-cell subgroup. RESULTS:OS differed significantly between monomorphic T-cell neoplasms (median, 9 months) and polymorphic, monomorphic B-cell, and Hodgkin-type neoplasms, for which the median OS was not reached (P = .0001). Significant differences in OS among B subgroups were not detected, but there was a trend toward decreased survival for patients with Burkitt-type PTLD. Kidney transplantation and a reduction of immunosuppression were associated with increased OS for patients with B-cell neoplasms in a multivariate analysis. Immunosuppression with azathioprine was associated with decreased OS for patients with T-cell neoplasms, whereas radiotherapy was associated with improved OS for patients with that subtype. CONCLUSIONS:The histologic subtype represents an important prognostic factor in PTLD, with patients with T-cell neoplasms exhibiting very poor OS. Possibly lower survival for certain subsets of patients with B-cell PTLD should be explored further and suggests the need for subtype-specific therapies to improve outcomes. Cancer 2018;124:2327-36. © 2018 American Cancer Society.

Project description:BackgroundHigh mortality rates have been reported in people released from prison compared with the general population. However, few studies have investigated potential risk factors associated with these high rates, especially psychiatric determinants. We aimed to investigate the association between psychiatric disorders and mortality in people released from prison in Sweden.MethodsWe studied all people who were imprisoned since Jan 1, 2000, and released before Dec 31, 2009, in Sweden for risks of all-cause and external-cause (accidents, suicide, homicide) mortality after prison release. We obtained data for substance use disorders and other psychiatric disorders, and criminological and sociodemographic factors from population-based registers. We calculated hazard ratios (HRs) by Cox regression, and then used them to calculate population attributable fractions for post-release mortality. To control for potential familial confounding, we compared individuals in the study with siblings who were also released from prison, but without psychiatric disorders. We tested whether any independent risk factors improved the prediction of mortality beyond age, sex, and criminal history.FindingsWe identified 47,326 individuals who were imprisoned. During a median follow-up time of 5·1 years (IQR 2·6-7·5), we recorded 2874 (6%) deaths after release from prison. The overall all-cause mortality rate was 1205 deaths per 100,000 person-years. Substance use disorders significantly increased the rate of all-cause mortality (alcohol use: adjusted HR 1·62, 95% CI 1·48-1·77; drug use: 1·67, 1·53-1·83), and the association was independent of sociodemographic, criminological, and familial factors. We identified no strong evidence that other psychiatric disorders increased mortality after we controlled for potential confounders. In people released from prison, 925 (34%) of all-cause deaths in men and 85 (50%) in women were potentially attributable to substance use disorders. Substance use disorders were also an independent determinant of external-cause mortality, with population attributable fraction estimates at 42% in men and 70% in women. Substance use disorders significantly improved the prediction of external-cause mortality, in addition to sociodemographic and criminological factors.InterpretationInterventions to address substance use disorders could substantially decrease the burden of excess mortality in people released from prison, but might need to be provided beyond the immediate period after release.FundingWellcome Trust, Swedish Research Council, and the Swedish Research Council for Health, Working Life and Welfare.

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Association of antiviral prophylaxis and rituximab use with posttransplant lymphoproliferative disorders (PTLDs): A nationwide cohort study.

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